Little is known about the hormonal control of prostate development. Previously, it was assumed that the development of the prostate was controlled primarily by testosterone. Recently, both insulin growth factor-I (IGF-I) and testosterone (T) were shown to be essential for development of the prostate gland, with the hormones working additively and/or synergistically, but also having independent effects (Ruan et al. (1999) Endocrinology 140:1984-1989).
The term “benign prostatic hyperplasia” (“BPH”) is generally used to represent clinical enlargement of the prostate or lower urinary tract symptoms including irritative or obstructive voiding pattern, urinary retention, and frequent urination with an increased residual urine volume. Benign prostatic hypertrophy is reported to occur in over 80% of the male population before the age of 80 years, and that as many as 25% of men reaching age 80 years will require some form of treatment, usually in the form of a surgical procedure (Partin (2000) Benign Prostatic Hyperplasia, in Prostatic Diseases (Lepor H. ed.), W.B. Saunders, Philadelphia, pp 95-105). While the cause has remained obscure, it is generally recognized that the two most important factors necessary for the induction of BPH are the presence of the testes and aging.
Several possible etiologies have been suggested as causing BPH, including testosterone, or a relative reduction in testosterone with an increase in estrogen. Treatment with 5α-reductase inhibitors, which reduce conversion of testosterone to dihydrotestosterone (the more active androgen for prostate growth), has been found to be only minimally effective in most patients. The adrenergic receptor antagonist, terazosin (Hytrin™) has been used to help symptoms of urinary obstruction caused by increased smooth muscle tone, but is found to be only temporarily effective and is associated with cardiovascular side-effects.
The role of excess GH and IGF-I on development of BPH and/or prostatic carcinoma was studied in patients suffering from acromegaly, a pituitary disorder caused in most cases by a GH-secreting adenoma (Colao et al. (1998) J. Clin. Endocrinol. Metab. 83:775-779). Compared to healthy subjects, a significant increase in transversal prostatic diameter and volume was observed in acromegalics. Colao et al. further disclose that symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were not experienced by acromegalics. Treatment with octreotide for 1 year induced normalization of circulating GH and IGF-I levels in most of the patients treated, as well as a reduction in prostate volume.
In light of the above, there is a need for a method for treating BPH that inhibits, prevents or reverses the progression of the disorder such that the need for surgical treatment is delayed or prevented.